scholarly journals Expression of cell markers and transcription factors in the avian retina compared with that in the marmoset retina

2021 ◽  
Author(s):  
Silke Haverkamp ◽  
László Albert ◽  
Vaishnavi Balaji ◽  
Pavel Němec ◽  
Karin Dedek
Keyword(s):  
Transcription Factors ◽  
Cell Markers ◽  
Avian Retina

Immunohistochemical Analysis of the Expression of the B- Cell Markers BCL-6, MUM1/IRF4, CD79A and Transcription Factors BOB.1 and OCT.2 in Classical Hodgkin Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 974-974
Author(s):  
S. Valsami ◽  
D. Rontogianni ◽  
V. Pappa ◽  
T. Economopoulos ◽  
F. Kontsioti ◽  
...  
Keyword(s):  
Transcription Factors ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Expression Pattern ◽  
Disease Free Survival ◽  
Classical Hodgkin Lymphoma ◽  
Time To Progression ◽  
Free Survival ◽  
Cell Markers ◽  
Disease Free

Abstract INTRODUCTION: Classical hodgkin’s lymphoma can be considered in most cases as a B-cell lymphoma by the presence of potentially functional immunoglobulin gene rearrangements in Hodgkin/Reed Sternberg (H-RS) cells However the expression of B cell markers in classical Hodgkin lymphoma is rare and the light and heavy chain mRNA is lacking. The exact mechanism for this discrepancy is not known, and some studies have suggested a transcription machinery deficiency. The aim of our study was the detection of B cell markers like CD79a, bcl6 and MUM.1/IRF4 in relation to B cell transcription factors BOB.1 and OCT.2 in classical Hodgkin lymphoma in order to define subgroups with different histogenesis and prognosis. Patients and methods: The analysis included 107 cases of classical Hodgkin lymphoma 55 males and 52 females with a median age of 37 (13–79). They were staged as: 17 stage I, 55 stage II, 13 stage III and 22 stage IV. Advanced stage patients were risk stratified according to the IPI, and early according to EORTC. The histological subtype was: Nodular sclerosis 76, Mixed cellularity 19, Lymphocyte depleted 5 and lymphocyte rich 7 cases. Extranodal disease was present in 24/107 (22.4%) cases. Diagnostic biopsies were used for histochemical detection of bcl/6, CD79a, MUM-IRF4 and B cell transcription factors BOB.1, OCT.2. Expression was considered as low if detected in 1–25%, medium in 26–49% and high in > 50% of H/RS cells. RESULTS Bcl6 was expressed in 22/101 cases, MUM.1 in 81/107 cases, BOB.1 in 89/100, OCT.2 in 17/100 and CD79a in 6/101 cases. In positive cases, bcl6, CD79a and OCT.2 have shown low expression, while MUM.1 and BOB.1 had a high expression in the majority of cases. There was not any difference in the expression pattern between different histologic subtypes for all these markers. Bcl6, MUM.1, OCT.2 and CD79a expression were not significantly different for different risk group categories and did not influence overall survival, disease free survival or time to progression. Cases positive for MUM expression had a significantly lower Hb (p=0.03), lower albumin (p=0.02), and higher IgG value (p=0.01). BOB.1 was expressed in 25% of early favourable, in 35% of intermediate and 40% of unfavourable early stage disease (p=0.06).There was a positive correlation between B symptoms and BOB.1 expression (p=0.01). There was a positive correlation between the expression of bcl6 and OCT.2 and between OCT.2 and CD79a (p=0.05, p=0.01) respectively. CONCLUSION MUM is expressed in the majority of classical Hodgkin lymphoma cases confirming its histogenesis from a late centrocyte and post/germinal centre B cell. B cell markers and transcription factors were not significant for survival, disease free survival and time to progression and their expression pattern was not different between different histological subtypes and risk groups of classical Hodgkin lymphoma.

scholarly journals Integrated Epigenetic and Transcriptional Single Cell Analysis of t(11;14) Myeloma and Its BCL2 Dependency

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 725-725
Author(s):  
Noemie Leblay ◽  
Sungwoo Ahn ◽  
Ranjan Maity ◽  
Holly Lee ◽  
Elie Barakat ◽  
...  
Keyword(s):  
Transcription Factors ◽  
B Cell ◽  
Single Cell ◽  
Plasma Cell ◽  
Copy Number ◽  
Acquired Resistance ◽  
Copy Number Gain ◽  
Chromatin Accessibility ◽  
Immunoglobulin Gene ◽  
Cell Markers

Abstract Multiple myeloma is characterized by recurrent chromosomal translocations that involve the immunoglobulin gene enhancers and partners such as the cyclin D genes (CCND1, CCND2 or CCND3) or other genes like WHSC1 and MAF. t(11;14) results in upregulation of CCND1 with unique morphological, phenotypic markers, and drug sensitivity profiles with exquisite sensitivity to BCL2 inhibitors. It is evident now that this unique sensitivity profile is driven by the BH3-proapoptotic protein priming of BCL2 with high BCL2/MCL1 or BCL2/BCL2L1 ratios. However, the epigenetic mechanisms associated with t(11;14) and their impact on genes regulation and clinical response to venetoclax remains elusive. In the present study we compared the transcriptomics (scRNA-seq) and chromatin accessibility (scATAC-seq) of single plasma cells of MM patients with and without t(11;14) as well as pre- and post-venetoclax exposure in order to establish the epigenomic signature of t(11;14) and/or BCL2-sensitivity in myeloma. Serial BM aspirates (n=24) were collected from 15 relapsed or refractory myeloma patients (RRMM); harboring t(11;14) (n=6 pairs) and 9 without this translocation prior to initiation of salvage therapy and at time of relapse. All t(11;14) MM patients were treated with venetoclax. Unbiased chromatin accessibility and mRNA profiling of CD138 pos cells were performed using the chromium single cell ATAC and RNA-Seq 3' solution (10x Genomics), respectively. Cell Ranger, Seurat and ArchR were used for sample de-multiplexing, barcode processing, single-cell 3' gene, peaks counting, and data analysis. We first compared the scATAC-seq and scRNA-seq profiles found in CD138 pos MM cell isolated from patients harboring t(11;14) with the one obtained in patients without this translocation. As expected, t(11:14) patients had high chromatin accessibility at the CCND1 locus and high mRNA expression. Differentially accessible chromatin analysis identified 147518 peaks that were specific to t(11;14) patients. Of interest, motifs enrichment analysis of accessible peaks identified a "B cell-like" motifs signature with enriched TFs motifs such as TCF4 and PAX5 in t(11;14) patients compared to non t(11:14) enriched for IRF and STAT family of motifs. The integration of the scATAC-seq and scRNA-seq data confirmed the B cell signature of t(11;14) patients with upregulation of B cell markers such as MS4A1, VPREB3, CD79A, CD19, and down-regulation of plasma cell markers such as TDO2, EFEMP1, CD28, SLAMF7, and IL6R. Additionally, we found PAX1, PAX5, TCF3, TCF5, and SPI1 transcription factors to be highly expressed in t(11;14) while the non t(11:14) were enriched for IRF1-9 transcription factors. Of interest, the clustering analysis performed on scATAC-seq data identified 3 non t(11;14) patients with a chromatin accessibility profile similar to that of t(11;14) patients. They expressed B cell markers (PAX5, VPREB3 or FCRLA), overexpressed BCL2 and we are currently examining whether this B cell-like epigenetic signature determines sensitivity to venetoclax. In order to define the epigenetic contribution to the acquired resistance to venetoclax in t(11;14) myeloma, we compared the chromatin accessibility profiles of t(11;14) patients pre- vs. post-venetoclax treatment. Enriched motifs within accessible peaks differed significantly between pre- and post-venetoclax with RELA, REL, RELB and EGR1 motifs predominantly enrichmed in the pre-samples in contrast to JUN, JUNB, JUND and FOSL1/L2 motifs enrichment in the post-samples. Of note, integration analysis of scRNAseq (differentially expressed genes) and ATACseq data (differentially accessible peaks) identified MCL1 and ENSA (a gene 60 Kb centromeric to MCL1 on chr1q) as the top enriched genes and peaks in resistant samples suggesting that copy number gain at the MCL1 locus (which we confirmed by single cell CNV analysis) rather than epigenetic modifications is likely the main determinant of acquired resistant to venetoclax in t(11;14) MM. In the current study we have defined the epigenetic regulome and transcriptome associated with t(11;14) myeloma and its relatedness to B cell rather than plasma cell biology. Our studies also suggest that acquired resistance to venetoclax is largely driven by copy number gain at the MCL1 locus. Disclosures Bahlis: Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Genentech: Consultancy; Pfizer: Consultancy, Honoraria. Neri: BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.

Expression of stem cell markers and transcription factors during the remodeling of the rat pancreas after duct ligation

2004 ◽  
Vol 446 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Katharina Peters ◽  
Roswitha Panienka ◽  
Jinming Li ◽  
G�nter Kl�ppel ◽  
Rennian Wang
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Stem Cell Markers ◽  
Rat Pancreas ◽  
Cell Markers ◽  
Duct Ligation

scholarly journals Reprogramming Mouse Cells With a Pancreatic Duct Phenotype to Insulin-Producing β-Like Cells

Endocrinology ◽  
2015 ◽  
Vol 156 (6) ◽  
pp. 2029-2038 ◽  
Author(s):  
Takatsugu Yamada ◽  
Claudia Cavelti-Weder ◽  
Francisco Caballero ◽  
Philippe A. Lysy ◽  
Lili Guo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pancreatic Duct ◽  
Fluorescent Protein ◽  
Cultured Cells ◽  
Β Cells ◽  
Β Cell ◽  
Cell Markers ◽  
Adenoviral Delivery ◽  
Glucagon Like Peptide 1 ◽  
Green Fluorescent

Abstract Reprogramming technology has opened the possibility of converting one cell type into another by forced expression of transgenes. Transduction of adenoviral vectors encoding 3 pancreatic transcription factors, Pdx1, Ngn3, and MafA, into mouse pancreas results in direct reprogramming of exocrine cells to insulin-producing β-like cells. We hypothesized that cultured adult pancreatic duct cells could be reprogrammed to become insulin-producing β-cells by adenoviral-mediated expression of this same combination of factors. Exocrine were isolated from adult mouse insulin 1 promoter (MIP)-green fluorescent protein (GFP) transgenic mice to allow new insulin-expressing cells to be detected by GFP fluorescence. Cultured cells were transduced by an adenoviral vector carrying a polycistronic construct Ngn3/Pdx1/MafA/mCherry (Ad-M3C) or mCherry sequence alone as a control vector. In addition, the effects of glucagon-like peptide-1 (GLP-1) receptor agonist, exendin-4 (Ex-4) on the reprogramming process were examined. GFP+ cells appeared 2 days after Ad-M3C transduction; the reprogramming efficiency was 8.6 ± 2.6% by day 4 after transduction. Ad-M3C also resulted in increased expression of β-cell markers insulin 1 and 2, with enhancement by Ex-4. Expression of other β-cell markers, neuroD and GLP-1 receptor, were also significantly up-regulated. The amount of insulin release into the media and insulin content of the cells were significantly higher in the Ad-M3C-transduced cells; this too was enhanced by Ex-4. The transduced cells did not secrete insulin in response to increased glucose, indicating incomplete differentiation to β-cells. Thus, cultured murine adult pancreatic cells with a duct phenotype can be directly reprogrammed to insulin-producing β-like cells by adenoviral delivery of 3 pancreatic transcription factors.

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